In vivo quantitative non-invasive dynamic monitoring of biochemical processes is one of the most difficult and important challenges in medical diagnostics. New near infrared (NIR) spectroscopy has been widely employed for this purpose. However, conventional methods generally do not separate light absorption from scattering, and as a result, do not report absolute biochemical concentrations in tissue. Advances in time and frequency domain NIR measurements have resulted in the development of quantitative approaches. However, these methods typically rely on a limited number of optical wavelengths and therefore have poor sensitivity to multiple analytes over a broad range of concentrations.
Traditional diagnostic methods for methemoglobinemia patients include pulse oximetry, arterial blood gas analysis, and co-oximetry. Pulse oximetry is, however, unreliable in the presence of methemoglobinemia since methemoglobin (MetHb) absorbs light equally well at wavelengths (typically 660 nm and 940 nm) used to determine oxygen saturation. Arterial blood gas analysis can be also misleading in methemoglobinemia because it will show normal partial pressure of oxygen even in the presence of high MetHb concentration and inaccurate oxygen saturation if values were calculated from the pH and PaO2. Co-oximetry is generally the principal laboratory technique used for the diagnosis of methemoglobinemia. Unfortunately, because co-oximetry relies on the absorption spectra of a few wavelengths for the calculation of MetHb concentration, false positive readings often result from the presence of other pigments such as methylene blue or sulfhemoglobin which have high absorption at the methemoglobin absorption peak at around 630 nm. Moreover, with co-oximetry, intermittent blood drawing is necessary and it is important to use fresh specimens for analysis as methemoglobin levels rise with storage time.
During the therapeutic stage of methemoglobinemia, methemoglobin can be reduced back to hemoglobin either enzymatically or non-enzymatically via a number of pathways. For drug-induced methemoglobinemia, methylene blue (MB) is a standard treatment modality. However, being an oxidant itself, large doses of methylene blue will overwhelm the reducing effect of leukomethylene blue, and can result in hemolysis and, paradoxically, methemoglobinemia in patients with glucose phosphate dehydrogenase (G6PD) deficiency. Unfortunately, the three aforementioned existing diagnostic methods (pulse oximetry, arterial blood gas analysis, and co-oximetry) are incapable of simultaneously quantifying in vivo tissue concentrations of MetHb and MB as well as oxyhemoglobin (Hb-O2) and deoxyhemoglobin (Hb-R) to monitor progression and resolution of methemoglobinemia.
There thus is a need for a method and device that can be used to dynamically monitor multiple in vivo tissue chromophores in a non-invasive manner. In addition, the method and device must have a sensitivity that is necessary from effective therapeutic monitoring. Preferably, there is a need for a method and device that permits real time or near real time concentration measurements of MetHb, Hb-R, Hb-O2, H2O, and MB. While a need exists for dynamically monitoring multiple chromophores to monitor progression and resolution of methemoglobinemia, it should be understood that needs also exist for additional diseased or abnormal states beyond methemoglobinemia. The device and method should be useful in evaluating the dynamics of drug delivery and therapeutic efficacy in blood chemistry. Preferably, the method and device can be used to dynamically monitor a variety of chromophores in vivo.